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United States Patent | 6,165,976 |
Backstrom ,   et al. | December 26, 2000 |
A therapeutic preparation for inhalation which comprises insulin and a substance which enhances the absorption of insulin in the lower respiratory tract, is provided in the form of a powder preparation suitable for inhalation.
Inventors: | Backstrom; Kjell Goran Erik (Lund, SE); Dahlback; Carl Magnus Olof (Lund, SE); Edman; Peter (Bjarred, SE); Johansson; Ann Charlotte Birgit (Lund, SE) |
Assignee: | Astra Aktiebolag (SE) |
Appl. No.: | 072717 |
Filed: | May 5, 1998 |
Current U.S. Class: | 514/3; 514/4; 530/303 |
Intern'l Class: | A61K 038/28; C07K 014/62 |
Field of Search: | 514/3,4 530/303 |
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TABLE I ______________________________________ Blood sample time after end of exposure Blood glucose Insulin conc. (minutes) (mmol/L) (.mu.U/ml) ______________________________________ before 3.9 6.70 0.5 3.6 120.66 5 2.8 194.47 10 2.6 195.39 20 n.d 139.74 22.5 1.6 n.d 31 2.0 73.42 45 1.7 47.49 59.5 1.7 36.21 89.5 2.3 19.28 120 3.0 14.58 240 4.5 5.28 ______________________________________ n.d. = not determined
TABLE II ______________________________________ Blood sample time after end of exposure Blood glucose Insulin conc. (minutes) (mmol/L) (.mu.U/ml) ______________________________________ before 3.9 44.84 3 4.2 165.10 6 4.3 158.28 12 3.9 n.d. 14 n.d. 180.72 19 3.0 133.75 30 2.7 143.71 45 2.5 91.62 60 2.4 66.70 90 2.7 38.58 122 3.7 29.15 241 4.1 n.d. 242.5 n.d. 19.76 ______________________________________ n.d. = not determined
TABLE III ______________________________________ Enhancer: Insulin: Substance lactose Effect ______________________________________ Octylglucopyranoside 4:4:92 (+) Sodium ursodeoxycholate 4:4:92 + Sodium taurocholate 4:4:92 + Sodium glycocholate 4:4:92 + Lysophosphatidylcholine 4:4:92 + Dioctanoylphosphatidylcholine 2:4:94 (+) Didecanoylphospatidylcholine 4:4:94 - Sodium taurodihydrofusidate 2:4:94 + Sodium caprylate 25:75:0 - Sodium caprate 10:90:0 (+) Sodium caprate 17.5:82.5:0 (+) Sodium caprate 25:75:0 + Sodium caprate 4:4:92 + Sodium laurate 25:75:0 (+) Potassium oleate 4:4:92 + Potassium caprate 27:73:0 + Lysine caprate 35:65:0 + Sodium myristate 30:70:0 + Dimethyl-.beta.-cyclodextrin 75:25:0 + ______________________________________ + significant decrease in blood glucose level (+) moderate decrease in blood glucose level - no or very small decrease in blood glucose level